Exposure to environmental neurotoxins is likely to increase the risk of developing neurodegenerative diseases, either directly or through interaction with genetic susceptibility factors. Work has begun to assess the role of environmental exposures in the etiology of these disorders. ALS is a progressive neurological disease affecting motor neurons; its etiology is essentially unknown. A protocol has been developed for a case-control study of the role of environmental risk factors in the etiology of ALS. The primary hypothesis is that cumulative lifetime exposure to lead is a risk factor for ALS. Lead exposure will be assessed by measuring bone lead, using the newly developed technology of x-ray fluorescence. Other environmental risk factors which will be investigated include mercury, solvents, and pesticides. Polymorphisms in genes which may increase susceptibility to lead or other neurotoxins will be also be studied. The study will involve interviews and clinical and laboratory assessments for 200 incident ALS patients and 200 clinical controls.